RECRUITING

An Open-label Study Comparing Lutetium (177Lu) Vipivotide Tetraxetan in Combination With ARPI Versus AAA617 in PSMA Positive First-line mCRPC

Conditions

Metastatic Castration Resistant Prostate Cancer (mCRPC)Prostate-specific membrane antigen (PSMA)lutetium (177Lu) vipivotide tetraxetan (AAA617)Androgen Receptor Pathway Inhibitors (ARPI)Enzalutamide Abiraterone Apalutamide Darolutamide

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The purpose of this study is to assess whether the combination of AAA617 (administered for 6 cycles at a dose of 7.4 GBq (200 mCi) +/- 10%) and ARPI improves radiographic progression-free survival (rPFS) or time to death compared to AAA617 alone in PSMA-positive mCRPC patients who were previously treated and progressed on ARPI in the biochemical recurrence (BCR)-non metastatic hormone sensitive prostate cancer (mHSPC), mHSPC, or non-metastatic Castration Resistant Prostate Cancer (nmCRPC) setting and have not previously received a taxane-containing regimen in the castrate resistant prostate cancer (CRPC) setting.

Official Title

A Phase II, Open-label, Multi-Center, Randomized Study Comparing the Combination of Lutetium (177Lu) Vipivotide Tetraxetan (AAA617) and Androgen Receptor Pathway Inhibitor (ARPI) vs. Lutetium (177Lu) Vipivotide Tetraxetan (AAA617) in First-line Treatment of Patients With Prostate-Specific Membrane Antigen (PSMA)-Positive Progressive Metastatic Castration Resistant Prostate Cancer (mCRPC)

Quick Facts

Study Start:2025-08-29

Study Completion:2029-04-09

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06894511

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 100 Years

Sexes Eligible for Study:MALE

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Participants must have an ECOG performance status of 0 to 2. * Participants must have histopathological, and/or cytological confirmation of adenocarcinoma of the prostate. * Participants must have PSMA PET positive disease using FDA approved PSMA-imaging approved agents, and eligible as determined by the sponsor's central reading rules. * Participants must have a castrate level of serum/plasma testosterone (\< 50 ng/dL or \< 1.7 nmol/L). * Newly diagnosed mCRPC participants who must have progression on prior ARPI in the BCR-non mHSPC, mHSPC, or nmCRPC setting. * Participants must have progressed only once on prior second-generation ARPI (abiraterone, enzalutamide, darolutamide, or apalutamide). First generation androgen receptor inhibitor therapy (e.g. bicalutamide) is allowed but not considered as prior ARPI therapy (second generation ARPI must be the most recent therapy received). * Participant must have been diagnosed with mCRPC with documented progressive disease after having been previously treated with ARPI in the BCR-non mHSPC, mHSPC, or nmCRPC setting as their last treatment (and did not progress on more than one ARPI), based on at least 1 of the following criteria: * Serum/plasma PSA progression is defined as 2 increases in PSA measured at least 1 week apart. The minimal start value is 2.0 ng/mL; 1.0 ng/mL is the minimal starting value if confirmed rise in PSA is the only indication of progression as per PCWG3 guidelines. * Soft-tissue progression defined \[PCWG3-modified RECIST v1.1 (Eisenhauer et al 2009, Scher et al 2016)\]. * Progression of bone disease: 2 new lesions; only positivity on the bone scan defines metastatic disease to bone (PCWG3 criteria \[Scher et al 2016\]). * Participants must have ≥ 1 metastatic lesion by conventional imaging that is present at Screening/Baseline CT, MRI, or bone scan imaging obtained ≤ 28 days (about 4 weeks) prior to randomization. * Participants must have adequate organ function: * Absolute Neutrophil Count (ANC) ≥ 1.5 × 109/L * Platelets ≥ 100 × 109/L * Hemoglobin ≥ 9 g/dL Hepatic * Total bilirubin \< 2 × the institutional upper limit of normal (ULN). For participants with known Gilbert's Syndrome ≤ 3 × ULN is permitted. * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 3.0 × ULN OR ≤ 5.0 × ULN for participants with liver metastases * Albumin ≥ 2.5 g/dL Renal * eGFR ≥ 50 mL/min/1.73m2 using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.	* Previous treatment with any of the following within 6 weeks of randomization: Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body irradiation, and Lu-DOTA radioligand therapy. * Previous PSMA-imaging RLT * Previous treatment with taxane-based chemotherapy at mCRPC settings. Taxane exposure is allowed in the mHSPC setting if more than 12 months have elapsed since the completion of this therapy. * Participants with a history of CNS metastases who are neurologically unstable, symptomatic, or receiving corticosteroids for the purpose of maintaining neurologic integrity. * Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression. * Participant with known or suspected deleterious germline or somatic homologous recombination repair gene-mutated mCRPC, who is considered appropriate for treatment with PARP inhibitor according to the judgment of the investigator. * History of myocardial infarction, angina pectoris, or coronary artery bypass graft (CABG) within 6 months prior to ICF signature and/or clinically active significant cardiac disease * Concurrent serious acute or chronic nephropathy as determined by the principal investigator.

Inclusion Criteria

Exclusion Criteria

* Participants must have an ECOG performance status of 0 to 2.
* Participants must have histopathological, and/or cytological confirmation of adenocarcinoma of the prostate.
* Participants must have PSMA PET positive disease using FDA approved PSMA-imaging approved agents, and eligible as determined by the sponsor's central reading rules.
* Participants must have a castrate level of serum/plasma testosterone (\< 50 ng/dL or \< 1.7 nmol/L).
* Newly diagnosed mCRPC participants who must have progression on prior ARPI in the BCR-non mHSPC, mHSPC, or nmCRPC setting.
* Participants must have progressed only once on prior second-generation ARPI (abiraterone, enzalutamide, darolutamide, or apalutamide). First generation androgen receptor inhibitor therapy (e.g. bicalutamide) is allowed but not considered as prior ARPI therapy (second generation ARPI must be the most recent therapy received).
* Participant must have been diagnosed with mCRPC with documented progressive disease after having been previously treated with ARPI in the BCR-non mHSPC, mHSPC, or nmCRPC setting as their last treatment (and did not progress on more than one ARPI), based on at least 1 of the following criteria:
* Serum/plasma PSA progression is defined as 2 increases in PSA measured at least 1 week apart. The minimal start value is 2.0 ng/mL; 1.0 ng/mL is the minimal starting value if confirmed rise in PSA is the only indication of progression as per PCWG3 guidelines.
* Soft-tissue progression defined \[PCWG3-modified RECIST v1.1 (Eisenhauer et al 2009, Scher et al 2016)\].
* Progression of bone disease: 2 new lesions; only positivity on the bone scan defines metastatic disease to bone (PCWG3 criteria \[Scher et al 2016\]).
* Participants must have ≥ 1 metastatic lesion by conventional imaging that is present at Screening/Baseline CT, MRI, or bone scan imaging obtained ≤ 28 days (about 4 weeks) prior to randomization.
* Participants must have adequate organ function:
* Absolute Neutrophil Count (ANC) ≥ 1.5 × 109/L
* Platelets ≥ 100 × 109/L
* Hemoglobin ≥ 9 g/dL Hepatic
* Total bilirubin \< 2 × the institutional upper limit of normal (ULN). For participants with known Gilbert's Syndrome ≤ 3 × ULN is permitted.
* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 3.0 × ULN OR ≤ 5.0 × ULN for participants with liver metastases
* Albumin ≥ 2.5 g/dL Renal
* eGFR ≥ 50 mL/min/1.73m2 using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.

* Previous treatment with any of the following within 6 weeks of randomization: Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body irradiation, and Lu-DOTA radioligand therapy.
* Previous PSMA-imaging RLT
* Previous treatment with taxane-based chemotherapy at mCRPC settings. Taxane exposure is allowed in the mHSPC setting if more than 12 months have elapsed since the completion of this therapy.
* Participants with a history of CNS metastases who are neurologically unstable, symptomatic, or receiving corticosteroids for the purpose of maintaining neurologic integrity.
* Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression.
* Participant with known or suspected deleterious germline or somatic homologous recombination repair gene-mutated mCRPC, who is considered appropriate for treatment with PARP inhibitor according to the judgment of the investigator.
* History of myocardial infarction, angina pectoris, or coronary artery bypass graft (CABG) within 6 months prior to ICF signature and/or clinically active significant cardiac disease
* Concurrent serious acute or chronic nephropathy as determined by the principal investigator.

Contacts and Locations

Study Contact

Novartis Pharmaceuticals

CONTACT

1-888-669-6682

novartis.email@novartis.com

Novartis Pharmaceuticals

CONTACT

Principal Investigator

Novartis Pharmaceuticals

STUDY_DIRECTOR

Novartis Pharmaceuticals

Study Locations (Sites)

Urology Cancer Center PC

Omaha, Nebraska, 68130

United States

Collaborators and Investigators

Sponsor: Novartis Pharmaceuticals

Novartis Pharmaceuticals, STUDY_DIRECTOR, Novartis Pharmaceuticals

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-08-29

Study Completion Date2029-04-09

Study Record Updates

Study Start Date2025-08-29

Study Completion Date2029-04-09

Terms related to this study

Keywords Provided by Researchers

Prostate-specific membrane antigen (PSMA)
lutetium (177Lu) vipivotide tetraxetan (AAA617)
Androgen Receptor Pathway Inhibitors (ARPI)
Enzalutamide
Abiraterone
Apalutamide
Darolutamide
metastatic Castration Resistant Prostate Cancer (mCRPC)

Additional Relevant MeSH Terms

Metastatic Castration Resistant Prostate Cancer (mCRPC)